NABNEC: A Randomised Phase II Study Of nab-Paclitaxel In Combination With Carboplatin As First Line Treatment Of Gastrointestinal Neuroendocrine Carcinomas

Neuroendocrine carcinomas (NEC, WHO 2010 grade 3 or PanNET, WHO 2017 grade 3), comprising small cell NEC and large cell NEC, are aggressive rare cancers and are generally rapidly fatal. They arise commonly in the gastrointestinal system. There have been a few retrospective studies, but no randomised, prospective controlled trials conducted to establish gold standard chemotherapy for advanced gastrointestinal NECs. The combination of etoposide and carboplatin has been the historical standard of care by extrapolation from small cell lung cancer trials. Paclitaxel and carboplatin are active in gastrointestinal NECs but there is no data on the role of nab-paclitaxel. This randomised study aims to determine the role of these therapies in clinical practice and to prospectively study the biology and imaging characteristics of NEC.

NABNEC began as an open label centrally 2:1 randomised multicentre phase II trial.  The study treatments were: Experimental arm: IV nab-paclitaxel (100 mg/m²) weekly and carboplatin (Area Under Curve [AUC]=5) every 3 weeks. Control arm: IV carboplatin AUC=5 on Day 1 and etoposide 100mg/m² on Days 1-3 every 3 weeks. The sample size is 58 patients.  A protocol amendment in February 2020 closed the control arm of the study after 12 patients had been randomised to this arm to reach an achievable statistically relevant trial result. There were a total of 48 patients enrolled onto the experimental arm of the trial.